The impact of transdermal testosterone treatment on quality of life in women with diminished ovarian reserve: secondary analysis of a randomized controlled trial

STUDY QUESTION
Does transdermal testosterone treatment improve fertility-related quality of life (QOL) in women with diminished ovarian reserve (DOR)?

SUMMARY ANSWER
Transdermal testosterone for 9 weeks at a dose of 5.5 mg per day did not result in improved fertility-related QOL compared with placebo in women with DOR.

WHAT IS KNOWN ALREADY
Reduced QOL is prevalent in women with infertility, many of whom have DOR. Several studies have shown a correlation between DOR and lower testosterone levels, and testosterone is frequently prescribed to women with DOR undergoing fertility treatment. Some studies have reported that testosterone therapy may improve wellbeing in pre- and post-menopausal women, though others have found no benefit. There are no studies evaluating the effect of testosterone on QOL in women undergoing fertility treatment.

STUDY DESIGN, SIZE, DURATION
Pre-planned secondary analysis of a double-blind placebo-controlled randomized controlled trial that included 288 participants recruited between April 2015 and August 2022. Of these, 213 completed QOL surveys both before and after treatment and were eligible for inclusion in this analysis.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS
Participants were women aged 18-43 years with DOR according to the Bologna criteria and planning to undergo IVF treatment at one of eight fertility clinics in Spain, Belgium, and Denmark. Participants were randomized to 5.5 mg of transdermal testosterone per day as 1% gel (n = 106) or an identical placebo (n = 107), applied for a median of 60 days prior to commencing ovarian stimulation. QOL was assessed using the FertiQoL instrument prior to commencing the intervention, and at the completion of the intervention but prior to commencing ovarian stimulation. QOL scores were compared using a one-way ANCOVA adjusted for age, BMI, parity, history of IVF treatment, and baseline FertiQoL scores.

MAIN RESULTS AND THE ROLE OF CHANCE
There were no significant differences in baseline characteristics between the testosterone (n = 106) and placebo (n = 107) groups. After adjustment, testosterone showed no benefit over placebo for the Total FertiQoL score (F(1,204)=0.07, P = 0.79), the Core and Treatment scores, nor for any of the included FertiQoL subscales. Total testosterone levels were higher in the testosterone group than the placebo group at the end of the treatment (3.2 ± 2.7 nmol/l vs 0.6 ± 0.4 nmol/l, P < 0.001).

LIMITATION, REASONS FOR CAUTION
QOL was a secondary outcome in this trial, and participants were not recruited based on a low QOL.

WIDER IMPLICATIONS OF THE FINDINGS
Considering the available evidence, including the current study, premenopausal women are unlikely to benefit from testosterone treatment with regard to wellbeing and QOL. This study provides further evidence that testosterone should not be seen as a treatment for low wellbeing or QOL.